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Higher-Order Protein Structure conference - Day 2

Higher Order Protein Structure 

Day 1 | Day 2 | Download Brochure | Short Courses 


8:00 am Registration and Morning Coffee



8:25 Chairperson’s Remarks

Erinc Sahin, Ph.D., Research Investigator, Biopharmaceutics, Drug Product Science & Technology, Bristol-Myers Squibb - Biography 

8:30 Case Study: Use of DSC in Higher-Order Structure Characterization and Prediction

Jie-WenJie Wen, Ph.D., Senior Scientist, Global Cellular & Analytical Resources, Amgen - Biography 

Differential scanning calorimetry (DSC) has been widely used by the biopharmaceutical industry for protein thermal stability and higher-order structure characterization. It is very sensitive to changes caused by the manufacturing process. At Amgen this technique has been successfully applied as a predictive tool for candidate screening and formulation development. This presentation will share the lessons learned from the case studies and discuss the qualification of this technique for protein thermal stability and higher-order structure characterization.

9:00 Higher-Order Structure Comparison of Biopharmaceuticals by Circular Dichroism: Definition of Unbiased Acceptance Criteria of Spectral Data

Horst-BierauHorst Bierau, Ph.D., Scientific Advisor & Relation Manager, Analytical Development Biotech Products, Merck Serono - Biography 

The use of Circular Dichroism for the analysis of higher-order structure of biopharmaceuticals is highlighted by case studies. One approach proposes to define unequivocal acceptance criteria, which eliminates operator bias associated with visual assessment of sample versus reference spectra. It is based on statistical analysis which distinguishes inherent variation in a given set of reference spectra from genuine structural differences that may be present in a sample. The proposed approach is generic and may readily be adapted to analyze spectral data obtained from techniques other than CD.

9:30 Effect of pH and Light on Aggregation and Conformation of an IgG1 mAb

Bruce-KerwinBruce Kerwin, Ph.D., Scientific Director, Drug Product Development, Amgen - Biography 

An IgG1 mAb at pH 3.5, 5 and 8 was exposed to UV light at multiple protein concentrations. The exposure resulted in a pH-dependent formation of high molecular weight species where the degree of oligomerization increased with increasing pH. The opposite trend was observed for conformational changes suggesting that different strategies will be required to stabilize the protein against these modifications during processing.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 The Characterizing Role of a Hydrophobic Patch in Antibody Clustering

Thomas Scherer, Ph.D., Scientist, Late Stage Pharmaceutical Development, Genentech - Biography  

It is well-known that relatively small discrepancies in protein surface electrostatics and hydrophobic area can lead to large differences in the strength of non-specific interactions and a protein’s structural stability, particularly at high concentrations. We have used biophysical, structural and analytical methods to improve our understanding of the issues encountered at high protein concentrations and their relationship to the macromolecular surface. Our current research on therapeutic antibodies has strong implications for using novel formulations to overcome common downstream drug product processing and delivery problems.

11:30 Structural Footprinting of a Homotetramer Using Chemical Cross-Linking and Mass Spectrometry

Jie-NanJie Nan, Ph.D., Wenner-Gren Fellow, Department of Molecular Biology, Uppsala Biomedical Center - Biography 

The structure of arginyltransferase is unknown and only distant homologs are found in the structural databases. Yeast arginyltransferase (yATE1) was recombinantly expressed and formed a stable homotetramer of ~400 KDa. Given no crystals after screening, chemical cross-linking and high-resolution mass spectrometry was applied to probe the structure. Over 200 unique cross-linked sites and nearly 90 single modification sites were identified. Further studies examining intra- and inter-protein cross-links provided distance restraints for structural modeling and tetramerization contacts.


Soluble And Insoluble Aggregates: Analytical Challenges 

» 12:00 pm Featured Presentation: 

New Methods for Therapeutic Protein Higher-Order Structure Characterization

Henryk-MachHenryk Mach, Ph.D., Senior Investigator, Bioprocess Analytical and Formulation Sciences, Merck Research Laboratories - Biography 

Changes in the process or formulation of therapeutic proteins and vaccines may bring unexpected changes in the propensity to aggregate despite favorable chemical and spectroscopic comparability. Development of precise and efficient methods to characterize the higher-order structure behavior during production and administration often requires adaptations of the existing hardware. 

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own 

1:55 Chairperson’s Remarks

Christopher Roberts, Ph.D., Associate Professor, Department of Chemical Engineering, University of Delaware - Biography 

2:00 Protein Aggregation: Experimental Approaches, Cautionary Observations & Kinetic Modeling

Erinc-SahinErinc Sahin, Ph.D., Research Investigator, Biopharmaceutics, Drug Product Science & Technology, Bristol-Myers Squibb - Biography 

Protein aggregation is recognized as one of the most significant stability problems that limit shelf life of biopharmaceuticals. Aggregates, being products of a continuum of oligomerization reactions, can vary between dimers to large polymers as well as soluble to insoluble materials. The variability in the length scales and solubilities of aggregates present formidable technical difficulties. This presentation includes experimental cases and cautionary observations that aim to challenge the way we look at aggregates, their characterization and formulation selection process.

2:25 Effect of polyols and mechanical stress on protein aggregation: How useful is DSC analysis?

Devendra KaloniaDevendra (Davy) Kalonia, Ph.D., Professor of Pharmaceutics, Department of Pharmaceutical Sciences, University of Connecticut - Biography 

2:50 Early Vaccine Functionary and Stability Prediction and Adapted Formulation Strategies

Olivier BrassOlivier Brass, Ph.D., Scientist, Discovery, Sanofi Pasteur - Biography 

The presentation will focus on how to develop vaccine formulation with innovative predictive tools. This will be illustrated by case studies on antigenic protein, adjuvanted glycoprotein, and lived attenuated virus. Rational predictive approaches for vaccine functionality and stability assessment, is a permanent challenge in order to assume an optimal time between product development and clinical trials and market launch.


3:15 Effects of Stress and Post-Translational Modifications on Protein Higher-Order Structure

Carl-JoneCarl Jone, Ph.D., Director, Analytical Development UCB - Biography 

The growing interest by regulators in protein higher-order structure, and whether protein structural variants are clinically relevant is driving a re-evaluation of current analytical methods and the development of novel techniques. The presentation will show how recent developments in higher-order structure analyses can reduce operator bias, facilitate understanding of structural changes of stressed molecules and demonstrate that post translational modifications may lead to changes in higher-order structure and influence biological activity.

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 NIST Standards for Counting and Characterization of Protein Particles: Status and Prospects

Dean-RippleDean Ripple, Ph.D., Leader, Bioprocess Measurements Group, National Institute of Standards and Technology - Biography 

To support the characterization of particles in protein therapeutics, NIST is developing polymer particle standards that closely mimic the optical properties of protein particles. We have created three types: 1) a polydisperse mixture of irregular particles formed by abrasion, 2) monodisperse particles formed by lithography, and 3) an optical ‘target’ with low-optical contrast features. These standards range in size from 1 µm to 300 µm, covering the design, formulation, stability and use, and characterization of each type.



4:45 Biophysical Characterization for Biosimilars: Comparability Studies and Technical Proof of Similarity

Otmar Hainzl, Ph.D., Lab Head, Biophysical Characterization, Analytical Characterization, Sandoz, Hexal AG - Biography 

Technical development of biosimilars requires continuous comparison with the originator product. As HOS analysis involves ensemble methods which show the overall status of a protein, as well as methods which can detect subtle differences between the product and originator material, it delivers comprehensive information on the protein. In a “technical proof of similarity” exercise, the analytical results are used to demonstrate required high similarity to the originator product, where HOS and binding studies may significantly improve understanding of the molecule and its mode of action.

5:15 End of Conference & Registration for Dinner Short Courses

6:00 – 9:00 pm Recommended Dinner Short Course* 

SC4 Sub-Visible Particle Analysis in High-Concentration Protein Formulations  

*Separate registration required 


Stay on to attend the sister conference focusing on High-Concentration Protein Formulations (Wed. – Thurs.)

Day 1 | Day 2 | Download Brochure | Short Courses 

Download Conference & Course Catalog

CHI Catalog March 2018 - August 2018 Cover